Mapping panels of somatic cell hybrids between rodent and human cells have been employed in an extensive series of mapping experiments to genetically locate a variety of human cellular genes which participate in neoplastic transformation. The hybrids, which were made with either normal or neoplastic human parent cells, segregate human chromosomes in different combinations. Seven distinct classes of neoplasia-related genes (with examples) have been studied and these include: (1) cellular proto-oncogenes which are sequentially homologous to retroviral or transfectionally active oncogenes (raf-1,2, Ha-ras-1, Ha-ras-2, Ki-ras-l, Ki-ras-2, ets, and rel); (2) growth factors (IL-2 or TCGF); (3) growth factor receptors (EGFR); (4) endogenous cellular DNA sequences homologous to retroviral RNA genomes (ERVI,2,3...); (5) integration sites for retroviruses (BEVI, HTLV-I); and (6) restriction genes which delimit retroviral replication in mammals. Within the last two years, the human gene map has experienced a large increase in the number of neoplasia loci which have been mapped to specific chromosomal positions. Of the 27 specific human loci which have been chromosomally mapped to date, ll (40%) of these have been assigned by the Genetics Section scientists and their collaborators. The construction of this extensive human map has played an important role in the resolution of early genetic events in neoplastic transformation in man. The genetic analysis of each of these loci has been considered in the perspective of the entire genome, of the rapidly advancing human gene map, and of the nonspecific chromosomal rearrangements characteristic of human malignancies. The emerging human gene map has provided, and continues to provide, an unprecented opportunity for molecular genetic analyses of the initiation and progression of neoplastic processes.